The lymphocytes were isolated from peripheral blood obtained under identical basal conditions in all subjects, allowing results from the two studies to be pooled. Unstimulated cAMP accumulation in lymphocyte incubates was similar in the three groups (Table 1). Isoprenaline enhanced cAMP accumulation approximately fivefold, the maximum response being reached at 10-5 M in most experiments (Table 1, Fig 1). The EC50 for isoprenaline varied considerably, but was about 5 to 10xl0“8 M, on the average (Table 1). IBMX enhanced basal and isoprenaline stimulated cAMP accumulation approximately fourfold in all three groups, without changing the EC^-values for isoprenaline. The cAMP-values for the prselective antagonist atenolol were similar in the three groups and four orders of magnitude higher than the cAMP-values for the nonselective (J-adrenoceptor antagonist propranolol (Table 1). Thus, lymphocytes from all three groups of subjects seemed to have a homogenous population of 02-adrenoceptors.

Lymphocytes from EIA patients showed a depressed cAMP response to isoprenaline (p<0.05) as compared to control subjects (Fig 1), whereas the response was normal in lymphocytes from NEIA patients compared to their matched controls (Fig 2), as well as to the entire control group flable 1). The cAMP–values for isoprenaline did not differ significantly between the groups (Table 1). Only one individual in the control group and one in the NEIA group had cAMP»-values for isoprenaline above 7 x 10“8 M (5.6 X10″ and 4.5 X10“7 M, respectively). In the EIA group, six out of 16 individuals had EC^-values for isoprenaline above 7xl0~8 M. Thus, the distribution of ECso-values for isoprenaline tended to be different in the three groups. You should buy asthma ventolin inhalers online only with one purpose to stop your attacks as quick as possible.

Responses to Isoprenaline Infusions

NEIA Patients (Study 1): The NEIA patients and control subjects of study 1 did not have significant bronchoconstriction and were approximately equal with regard to most physiologic variables 30 minutes after the exercise test which was performed in study 1. In this study, isoprenaline infusions were given at two rates (0.02 and 0.1 jig X kg‘1X min) which produced isoprenaline concentrations in plasma of 0.64 ±0.10 and 3.33±0.87 nM, respectively, in the control group and similar values in the NEIA group. There was no evidence of reduced responsiveness to isoprenaline, ventolin inhalers in vivo in the NEIA group. Thus, heart rate was increased from 77 ±4 to 133 ±2 beats per minute and diastolic blood pressure was reduced from 73 ± 4 to 39 ± 5 mm Hg in the NEIA group. The corresponding figures for their matched controls were 70 ± 4 to 129 ± 6 beats per minute and 77 ±3 to 41 ±4 mm Hg. Similarly, there were no differences between the groups with regard to plasma cAMP or glycerol responses. Since both the in vivo responses and the lymphocyte cAMP responses to isoprenaline (Fig 2) were normal in the NEIA patients, this patient group was not studied further.

EIA Patients (Study 2): The results from isoprenaline infusion tests in study 1, as well as the lymphocyte studies, had suggested that (adrenoceptor responsiveness might be reduced in EIA. Since the EIA patients were not basal at the time of the isoprenaline infusions in study 1, another eight EIA patients were recruited for farther studies of responsiveness to isoprenaline in vivo and in vitro.

Figure 3 summarizes the changes in cAMP and glycerol concentrations in plasma and in heart rate and diastolic blood pressure observed in study 2. The basal values for these and other variables were similar in the two groups, with the exception of Sgaw which was significantly lower in the EIA group (Table 2). Isoprenaline infusions enhanced the isoprenaline concentrations in plasma dose-dependently in both groups, the EIA group achieving somewhat higher concentrations at each dose level (eg, 1.91 ±0.19 vs 1.50±0.25 nM at 0.05 ^gxkg^xmin’). The interindividual variability in isoprenaline concentrations was approximately fivefold to sixfold. It may be seen that the heart rate and plasma glycerol responses to isoprenaline were virtually identical, whereas the plasma cAMP and diastolic depressor responses were significantly attenuated in the EIA group when plasma concentra-don-response curves were compared (Fig 3). If isoprenaline dose-response curves were compared, there was still a significant difference with regard to the diastolic depressor response, but not the plasma cAMP response.

Isoprenaline did not influence airways conductance in the control group, but induced significant bron-chodilatation in the EIA group at the intermediate and high dose levels (Fig 4). Plasma noradrenaline increased similarly in the two groups (to 2.77±0.33 nMin EIA patients and 2.95 ±0.18 nM in controls at the intermediate dose level; no further increase was seen at the high dose level), but adrenaline did not increase during isoprenaline infusions.

Figure 1. Isoprenaline induced accumulation of cAMP in lymphocytes from 16 EIA patients and 15 healthy matched controls. The dose-response curve obtained in the EIA group differed from that obtained in the control group (p<0.05), when compared by analysis of covariance.

Figure 3. Changes in plasma cAMP and glycerol, heart rate (HR) and diastolic blood pressure (DBP) in relation to venous plasma isoprenaline concentrations in eight EIA patients (from study 2) and seven matched healthy control subjects. The p2-mediated responses of plasma cAMP and diastolic blood pressure were significantly reduced in EIA (p<0.05 for both responses when concentration-effect curves were compared by analysis of covariance). The mainly Pr or mixed P^-mediated responses of heart rate and plasma glycerol did not differ between the groups.

Figure 4. Specific airway conductance (Sgaw) in the EIA group of study 2 and their matched control subjects before and during isoprenaline infusion. *p<0.Q5, **p<0.01, as compared to basal values.